Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model.
Journal:
Nat. Genet. 2008 JunAuthors:
Stark KL, Xu B, Bagchi A, Lai WS, Liu H, Hsu R, Wan X, Pavlidis P, Mills AA, Karayiorgou M, Gogos JA
Abstract
Individuals with 22q11.2 microdeletions show behavioral and cognitive deficits and are at high risk of developing schizophrenia. We analyzed an engineered mouse strain carrying a chromosomal deficiency spanning a segment syntenic to the human 22q11.2 locus. We uncovered a previously unknown alteration in the biogenesis of microRNAs (miRNAs) and identified a subset of brain miRNAs affected by the microdeletion. We provide evidence that the abnormal miRNA biogenesis emerges because of haploinsuffi
...[more]ciency of the Dgcr8 gene, which encodes an RNA-binding moiety of the 'microprocessor' complex and contributes to the behavioral and neuronal deficits associated with the 22q11.2 microdeletion.[less]
Mesh Headings:
Animals, Behavior, Animal, Brain, Chromosome Deletion, Chromosomes, Human, Pair 22, Cognition Disorders, Disease Models, Animal, Female, Gene Expression Profiling, Habituation, Psychophysiologic, Heterozygote, Humans, Learning Disorders, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, MicroRNAs, Oligonucleotide Array Sequence Analysis, Phenotype, Proteins, Sensation Disorders, Spine